The value of and need for routine RNA oligonucleotide synthesis has been rapidly increasing over the past decade as research reveals the extent of RNA's biological functions. Current methods enable the synthesis of RNA in acceptable yields and quality, but a high level of skill appears to be required to deliver adequate results. The focus of this NIH SBIR Phase II project is to enable a powerful new RNA synthesis technology to be readily accessible to the scientific community. The specific aims will be achieved with the following research plan: Nucleoside chemistry Optimizations of 5'- and 3'-reagents and reactions Application of synthesis methods in other labs and to modified bases Development of economical large scale phosphoramidite synthesis Oligonucleotide synthesis chemistry Standardization of reagents, modifications and methods on current instrument Testing and evaluation in collaborating independent labs Optimization of 2'-ACE chemistry on other standard synthesis instruments The successful execution of this research plan will provide the general synthesis instruments with a readily available and reliable means of synthesizing high quality RNA oligonucleotides. With a ready means of synthesizing RNA oligonucleotides, it is expected that research and health-related discoveries will follow. PROPOSED COMMERCIAL APPLICTION: NOT AVAILABLE